psoriatic arthritis treated with liraglutide therapy: a quality of life and efficacy study

Conditions: Psoriatic Arthritis; Psoriasis; Impaired Glucose Tolerance; Type 2 Diabetes

Summary: exploratory, double-blind randomized, placebo-controlled, phase ii study to evaluate the effect(s) of short-term administration of liraglutide, a glp-1r (glucagon-like peptide-1 receptor) agonist on joint and skin inflammation in patients with active psoriatic arthritis.

the primary purpose of this study is to determine whether short-term (12-week) administration of the glp-1r agonist, liraglutide, will improve joint and skin swelling in patients with active psoriatic arthritis compared to placebo. background: psoriatic arthritis is a systemic inflammatory t-cell disorder affecting the joints and spine, and is associated with an elevated risk for type 2 diabetes and cardiovascular disease. in addition to classical effects on glycemic-lowering, glp-1r agonists are anti-diabetes agents which also have anti-inflammatory properties that may be clinically useful for patients with inflammatory diseases, particularly those with co-morbid metabolic disease. while a few small exploratory studies in patients with psoriasis have demonstrated that glp-1r agonists reduce the severity of skin plaques, dedicated prospective, randomized mechanistic studies evaluating potential mechanisms by which glp-1r agonists exert anti-inflammatory action(s) in humans with inflammatory disease is lacking. objectives: primary objective is to evaluate the clinical efficacy of short-term liraglutide (glp-1r agonist) administration on the severity of joint and skin inflammation in patients with active psoriatic arthritis. secondary objectives are to determine whether short-term liraglutide administration in patients with active psoriatic arthritis will 1) modify the degree of impaired glucose tolerance, underlying b-cell function and cardiovascular risk factor profiles, 2) improve patient-centered outcomes such as quality of life and functionality, 3) modify specific sub-populations of t-cells and affect their differentiation and activation, and 4) modify activation of circulating immune cells, pro-inflammatory cytokines, and hormones. design: double-blind, randomized, placebo-controlled trial, phase ii. patient population: 34 patients between with active psoriatic arthritis meeting caspar (classification criteria for psoriatic arthritis). intervention: participants will be randomized (1:1) to liraglutide (1.2 mg sc daily) or to placebo (sc daily) for 12 weeks. endpoints: the primary endpoint of this study will be the proportion of patients who experience a 20% acr (american college of rheumatology) improvement response following liraglutide therapy as compared to placebo.

Eligibility criteria:
inclusion criteria: * patients with active psoriatic arthritis (3 tender and swollen joints) meeting caspar study group criteria exclusion criteria: * bmi \> 35 kg/m2 * uncontrolled diabetes, hba1c \> 10.5% * current biological treatment for any inflammatory disorder within the past three months * renal dysfunction (egfr \ 300mg) * hepatic dysfunction (ast (aspartate aminotransferase), alt (alanine aminotransferase), total bilirubin \> 3 times upper limit of normal) * history of pancreatitis or personal or family history of medullary thyroid cancer, c-cell hyperplasia, or men-2 syndrome * current pregnancy or current breast feeding * use of dpp-4 (dipeptidyl peptidase-4 inhibitor) or glp-1 receptor agonist within 2 months (washout is permitted) * drug or alcohol dependence * resting tachycardia \> 100 bpm or conduction abnormalities associated with tachycardia * current enrollment in any other clinical trial * symptomatic gastroparesis * concomitant serious medical conditions * all medication for the treatment of psoriatic arthritis such as mtx (methotrexate) \< 25 mg, lfn (leflunomide) \< 20 mg, and nsaids (non-steroidal anti-inflammatory drugs) will have been used at stable doses for at least 4 weeks, having been initiated at least 3 months prior to study start (8 weeks before screening, 4 weeks before baseline) for mtx and lfn and at least 4 weeks for nsaids

Keywords: liraglutide, glp-1 receptor agonists